Cyclo<(N-L-prolyl-N-methyl-D-leucyl)-O-<oxy>-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl> | 120286-05-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: Cyclo<(N-L-prolyl-N-methyl-D-leucyl)-O-<oxy>-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl>
• 英文别名: N-(L-Pro)didemnin A；N-prolyl-didemnin A；(2S)-N-[(2R)-1-[[(3S,6S,8S,12S,13R,16S,17R,20S,23S)-13-[(2S)-butan-2-yl]-12-hydroxy-20-[(4-methoxyphenyl)methyl]-6,17,21-trimethyl-3-(2-methylpropyl)-2,5,7,10,15,19,22-heptaoxo-8-propan-2-yl-9,18-dioxa-1,4,14,21-tetrazabicyclo[21.3.0]hexacosan-16-yl]amino]-4-methyl-1-oxopentan-2-yl]-N-methylpyrrolidine-2-carboxamide
• CAS: 120286-05-7
• 化学式: C₅₄H₈₅N₇O₁₃
• 分子量: 1040.31
• InChiKey: MMUFNCTVUTWOJE-OUWSPRRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  74
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  259
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  (2S,4R)-Cbz-4-甲磺酰氧基脯氨酸甲酯 在 palladium on activated charcoal N-甲基吗啉 、 吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 四丁基氟化铵 、 氢气 、 双氧水 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -15.0~25.0 ℃ 、275.79 kPa 条件下， 反应 43.0h， 生成 Cyclo<(N-L-prolyl-N-methyl-D-leucyl)-O-<oxy>-3-oxo-2,5-dimethylhexanoyl>-L-leucyl>-L-prolyl-N,O-dimethyl-L-tyrosyl>-L-threonyl>
  参考文献：
  名称：

  Synthesis of New Didemnin B Analogs for Investigations of Structure/Biological Activity Relationships

  摘要：

  Modifications were introduced in the side chain of didemnin B to afford several analogs (1f-1j) for biological testing in order to identify the features responsible for the bioactivity of the natural products (1a-1c). To achieve our goal, two changes were made in the proline ring of the beta-turn side chain. Initially, a hydroxyl group was incorporated at the C-4 position of the ring to increase the polar nature of the molecule. Secondly, unsaturation was introduced at C-3 and C-4 to increase the rigidity of the ring and to provide a site for tritiation to follow the drug pathway in biological systems. Improvements were also introduced in the macrocycle construction to produce gram quantities of this unit (1d) for the preparation of the planned analogs. The linear precursor to the macrocycle was oxidized more effectively with 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent), and cyclization yields were increased substantially by using a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP). (1H-1,2,3-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and pentafluorophenyl trifluoroacetate were also used to improve other coupling reactions.

  DOI：

  10.1021/jo00097a022

文献信息

• Structure−Activity Relationships of the Didemnins
  作者：Ryuichi Sakai、Kenneth L. Rinehart、Vimal Kishore、Bijoy Kundu、Glynn Faircloth、James B. Gloer、John R. Carney、Michio Namikoshi、Furong Sun、Robert G. Hughes,、Dolores García Grávalos、Teresa García de Quesada、George R. Wilson、Richard M. Heid

  DOI：10.1021/jm960048g

  日期：1996.1.1

  Bioactivities of 42 didemnin congeners, either isolated from the marine tunicates Trididemnun solidum and Aplidium albicans or prepared synthetically and semisynthetically, have been compared. The growth inhibition of various murine and human tumor cells and plaque reduction of HSV-1 and VSV grown on cultured mammalian cells were used to assess cytotoxicity and antiviral activity. Biochemical assays for macromolecular

  比较了从海生被膜Trididemnun solidum和Aplidium Albicans分离或合成和半合成制备的42种双氢精蛋白同类物的生物活性。各种鼠类和人类肿瘤细胞的生长抑制作用以及在培养的哺乳动物细胞上生长的HSV-1和VSV的噬斑减少用于评估细胞毒性和抗病毒活性。还进行了大分子合成（蛋白质，DNA和RNA）和酶抑制（二氢叶酸还原酶，胸苷酸合酶，DNA聚合酶，RNA聚合酶以及拓扑异构酶I和II）的生化分析，以阐明每种类似物的作用机理。使用混合淋巴细胞反应（MLR）测定法确定双氢辅酶的免疫抑制活性。这些测定法揭示了天然环状二肽肽核心是双嘧达明的大部分生物活性的基本结构要求，特别是对于细胞毒性和抗病毒活性。在某些情况下，可以通过增加生物活性来改变肽的线性侧链部分。特别是针对小鼠的几种类型的肿瘤细胞和体内研究测试的脱氢美地那宁B，以及针对鼠类系统中混合淋巴细胞反应和移植物与宿主反应的测试
• Total synthesis of the didemnins - 2. Synthesis of didemnin A, B, C and prolyldidemnin A
  作者：U. Schmidt、M. Kroner、H. Griesser

  DOI：10.1016/s0040-4039(00)80507-9

  日期：1988.1

  Didemnin A, C, prolyldidemnin A and the highly cancerostatic, antiviral and immunosuppressive didemnin B have been prepared by deprotecting the benzyloxycarbonyl compound 5 and constructing the side chain that determines the biological properties.

  通过使苄氧羰基化合物5脱保护并构建决定生物学特性的侧链，制备了二氢肌酐A，C，脯氨二醛A以及高度抗癌，抗病毒和免疫抑制的二氢肌酐B。
• SCHMIDT, U.;KRONER, M.;GRIESSER, H., TETRAHEDRON LETT., 29,(1988) N 35, C. 4407-4408
  作者：SCHMIDT, U.、KRONER, M.、GRIESSER, H.

  DOI：——

  日期：——